Microscopic examination of tissue samples, particularly those obtained by biopsy, is a common method for diagnosis of disease. In particular, immunohistochemistry (IHC), a technique in which specific antibodies are used to detect expression of specific proteins in the tissue sample, may be a valuable tool for diagnosis, particularly for the detection and diagnosis of cancer.
The Sry-related HMG-Box gene 10, perhaps located at chromosome 22q13, may encode a protein known as SOX 10, which is perhaps a transcription factor in humans that may be important for neural crest, peripheral nervous system, and melanocytic cell development. SOX10 may be essential for the formation of nerves in the large intestine and melanocytes. Melanocytes are perhaps cells that produce pigment, found in the skin, eyes, and hair. The SOX10 protein may be widely expressed in human normal tissues including melanocytes, breast tissue, cranial ganglia, dorsal root ganglia, and the optic vesicle. SOX10 may perhaps also be an important marker in malignant tumors such as melanoma, breast carcinoma, gliomas, and the like, as well as benign tumors such as schwannomas, and the like. The transcriptional factor SOX10 may be one of the key determinants of oligodendroglial differentiation. The majority of oligodendrogliomas, but also a large fraction of astrocytomas, including the least differentiated glioblastomas, perhaps express SOX10.
Desmoplastic melanoma may be a rare variant of invasive cutaneous melanoma, with an annual incidence rate of perhaps approximately 2 per 1,000,000. Features unique to this melanoma type may include deep invasion, increased peri-neural invasion, local recurrence and perhaps delayed diagnosis. Studies may have shown that SOX10 is a highly sensitive and specific marker of melanoma in both primary and metastatic lesions. On the basis of the expression in melanocytes of non-neoplastic and benign skin, and in benign and dysplastic nevi, SOX10 may not be a useful marker to differentiate between benign and malignant pigmented skin lesions.
Desmoplastic melanoma (DM) may present diagnostic challenges perhaps due to similarity of histologic mimics and even perhaps limited immunohistochemical staining. In one study, SOX10 may have shown 100% sensitivity for DM and perhaps SOX10 was negative in all histologic mimics of the dermis/subcutis, including spindle cell carcinoma, AFX and sarcomas. Although anti-S100 antibodies may typically stain DM, other melanoma markers (e.g. HMB-45 and Melan-A) are perhaps often negative.
Traditionally, melanoma markers such as S100, HMB45, MART-1 (perhaps also known as Melan-A), and Tyrosinase may have been used in a panel of antibodies to identify melanoma. Anti-S100 antibody may have been used as a screener for melanoma, and perhaps may have been a more sensitive marker compared to other melanoma markers; however, S100 may have a disadvantage of suboptimal specificity as it may stain both lymph nodes and brain, which are common sites of metastatic melanoma and its mimics. HMB45, MART-1 and Tyrosinase may perhaps be more specific than S100 protein; however, this panel of antibodies may be negative in desmoplastic melanoma and spindle cell melanoma and thus perhaps lack sensitivity.
An antibody cocktail of MART-1 and Tyrosinase, may have been shown to be a very sensitive marker of metastatic melanomas and perhaps even comparable to S100 protein (about 98% versus about 100%, respectively). However, S100 may have still been more sensitive for desmoplastic melanoma and spindle cell melanoma. The potential benefit of combining SOX10, with its sensitivity for melanoma, including desmoplastic melanoma and spindle cell melanoma, and one or more melanoma markers, perhaps even those that are not sensitive for desmoplatic melanoma or spindle cell melanoma, including perhaps MART-1 and Tyrosinase, may not be known. Such a combination may provide a superior marker for melanoma.
SOX10 may also be a neural crest transcription factor crucial for specification, maturation, and maintenance of Schwann cells and melanocytes. SOX10 may also be diffusely expressed in schwannomas and neurofibromas. Despite perhaps a well-characterized lack of specificity, pathologists may routinely employ S100 in the diagnosis of neural crest-derived tumors. Recent studies have shown that perhaps SOX10 is a reliable marker of neural crest differentiation that may be consistently expressed in schwannian and melanocytic tumors, perhaps offering advantages over S100.
SOX10 expression may be observed in myoepithelial breast cells in normal breast glands. SOX10 may have been demonstrated in basal-like, unclassified triple-negative, and in metaplastic carcinoma breast cancer types; and perhaps supports the concept that these neoplasms may show myoepithelial differentiation. In lung cancers, sustentacular cells may be found in approximately half of pulmonary carcinoid tumors. A SOX10 antibody was used to investigate perhaps 113 pulmonary cases that we not elsewhere classified (NEC). Sustentacular cells may have been observed in perhaps 66.7% of typical carcinoid (TC) and even perhaps 58.3% of atypical carcinoid (AC) cases, but may not have been observed in high-grade NECs.
SOX10 may show an increased specificity for tumors of neural crest origin, when perhaps compared with S100. In one study, SOX10 may have been positive in perhaps only 5 of 668 cases (99% specificity) in non-schwannian, non-melanocytic tumors, whereas S100 may have been positive in perhaps 53 of 668 cases (91% specificity). Therefore, SOX10 may be useful in place of, or perhaps in combination with S100, for soft tissue tumor diagnosis.
To date, most published studies may have used a goat polyclonal SOX10 for immunohistochemical (IHC) methods. Polyclonal goat antibodies may not be generally preferred for use in IHC methods, as monoclonal antibodies may be preferred, even perhaps mouse or rabbit antibodies may be preferred. Particularly for the IHC methods used in clinical diagnosis, monoclonal antibodies may be preferred, perhaps even mouse or rabbit antibodies are preferred. A clear need may exist for a marker to differentiate spindle cell and desmoplastic melanoma from other tumors and its mimics and perhaps extensive efforts to date may not have yielded such a marker. A SOX10 monoclonal antibody, would perhaps be highly valuable in the clinical setting for diagnosis.
Therefore, a clear need exists for a sensitive and even specific anti-SOX10 antibody for use in cancer diagnosis. Embodiments of the present invention provide an anti-SOX10 mouse monoclonal antibody [clone BC34] which may be highly sensitive and may even be highly specific. An example of the present invention provides a mouse monoclonal anti-SOX10 antibody that may detect the presence or absence of SOX10 protein in certain cancers, including but not limited to melanoma, spindle cell melanoma, desmoplastic melanoma, nevi, schwannomas, breast cancer, rhabdomyosarcoma, leiomyosarcoma or the like. An example of the present invention may have demonstrated excellent sensitivity for melanoma (about 105/109, about 9%) with perhaps even excellent specificity versus other normal, benign and malignant tissues. When compared to the known rabbit polyclonal (RP) anti-SOX10 antibody, the mouse monoclonal anti-SOX10 BC34 may have typically demonstrated greater sensitivity, and perhaps greater specificity, with cleaner staining patterns, perhaps with fewer artifacts, and perhaps without staining many carcinoids, while even offering the advantages of a monoclonal antibody. BC34 also may not stain some specimens, which may have been stained by the RP anti-SOX10 antibody, perhaps indicating the superior specificity of BC34 over alternatives. Therefore, a monoclonal anti-SOX10 antibody, such as BC34, may be preferred for diagnosis, compared to alternative antibodies, including alternative anti-SOX10 antibodies.
The development of an anti-SOX10 antibody may aid in the diagnosis of primary and even metastatic cancers, particularly melanoma, spindle cell melanoma, desmoplastic melanoma, nevi, schwannomas, breast cancer, rhabdomyosarcoma, leiomyosarcoma or the like. Anti-SOX10 antibodies such as mouse monoclonal anti-SOX10 antibody [BC34], with perhaps equal or superior staining sensitivity, and perhaps even superior staining specificity such as compared to alternative anti-SOX10 antibodies, including the RP anti-SOX10 antibody, have been provided in the present invention.